Prof Madhavi Krishnan

Research

Soft condensed matter at the nanometer scale

In our group we focus on measuring, understanding and controlling molecular-level interactions and transport at the nanometer scale in fluids. A major current interest is the electrostatic interaction which is strong and long-ranged in fluids, and ubiquitous in chemical and biological systems. Using the familiar repulsive force between like-charged entities we recently demonstrated the ability to stably trap single molecules in solution in three dimensions. Our use of equilibrium thermodynamics to achieve this long-standing experimental goal is a paradigm shift in a century-old effort that relied nearly exclusively on externally applied electromagnetic fields to control and manipulate matter all the way from ions to large particles.

In contrast to our generally static macroscopic experiential world, a microscopic bit of matter in solution is in continuous motion. Pummelled at random by the solvent, it engages in a Brownian walk that will eventually take it far away from where we first started to observe it. At the nanoscale, even applied fields, much like gravity, are too weak to substantially influence the trajectory of the object. Placing surfaces in the vicinity however puts new forces into play. By appropriately tailoring the geometry of the walls we are able to harness these intrinsic object-surface forces and manoeuvre our entity of interest into a desired spatial location and orientation in a fluid. Once there, the object levitates stably for long periods (see movie below).

A field-free trap for a single molecule in solution

Pictorial representation of a nanostructured parallel-plate system capable of trapping a single molecule in solution (left). Movie of a single fluorescently labeled intrinsically disordered protein trapped for ~30 min in an electrostatic fluidic trap; single particle tracking reveals the centre-of-mass of the trapped molecule as a function of time (central panels). On the right - a calculation of the spatial distribution of electrostatic energy, U in an electrostatic fluidic trap. The calculation illustrates how a height perturbation in a parallel-plate system composed of charged walls gives rise to a local potential minimum for a like-charged object in solution.

We are pioneering the use of the electrostatic fluidic trap in order to realize new experiments in the spatial control, manipulation, and measurement of nanoscale matter in solution. We recently used the trap to demonstrate two conceptual breakthroughs in nanoscience: (1) the realization of a "digital colloid", or a freely levitating nanoparticle as an information storage medium, and (2) the measurement of the electrical charge of a single macromolecule with sub-elementary-charge precision.

Since electrostatics plays a fundamental role as an interaction mechanism at the molecular scale, but has yet remained relatively unexplored terrain at the experimental level, new lines of activity unfolding in our lab take a microscopic experimental and theoretical view of electrical charge in macromolecules. One of these directions focuses on understanding the relationship between a molecule's electrical charge and its three dimensional conformation, and we address this question by asking for the first time if a high-precision electrical charge measurement in real time can read out three-dimensional conformational changes or fluctuations in a single macromolecule in solution.

​Escape-time electrometry (ETe) is a new experimental technique we have developed that enables the measurement of the effective electrical charge of a single molecule with sub-elementary charge precision. On the right is a video showing a blue-labelled 60 bp DNA molecule and a green-labelled 50 bp DNA molecule thermally sampling a lattice of electrostatic traps. Rapid escape of the green molecule - evident even in casual observation - shows that it carries much less charge than its comparatively sluggish blue counterpart. The movie is slowed down by a factor 2.

Beyond potentially making their way into practical devices such as ultra-sensitive and highly precise molecular sensors - possibly even memories and displays - our findings are continually pushing the envelope on control, manipulation, and fundamental measurement and understanding of matter at the nanometer scale.